Breakthrough In Lung Transplant Biomedicine

Original story by Ker Than

Edited by Cathleen V. Carr, JD PhD, a National Health Channel reporter for Examiner.com

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There has been a breakthrough in biomedical engineering that could lead to replacement lungs for humans in the near future, experts say.

For the first time scientists have reconstructed working lungs in the lab and transplanted them into a living animal- a rat.

In a new study, researchers took lungs from a living rat and used detergents to remove lung cells and blood vessels, revealing the organ's underlying matrix.The researchers placed these lung cells into a bioreactor, a machine filled with a slurry containing different types of lung cells extrated from rat fetuses.  Within several days the fetal cells naturally attached to the lung matrix and formed a functional lung.

Study leader Laura Niklason, a biomedical engineer at Yale University said, "It appears that the lung matrix has cues, or 'zip codes,' that tell the cells where to land."

When the team implanted the engineered lungs into an adult rat for short periods of time—between 45 minutes and two hours—the lungs exchanged oxygen and carbon dioxide in the same way as natural lungs.

Such “site-specific” cell development has never been seen before in a natural matrix, said professor Joan Nichols, another of the paper’s lead authors. The complexity gives the researchers hope that the concept could be scaled up to produce replacement tissues for humans — or used to create models to test therapies and diagnostic techniques for a variety of lung diseases.

By using a natural lung matrix, Niklason's team has avoided one of the biggest hurdles of lung-regeneration attempts—finding a suitable "scaffold" for lung cells to attach to. Because manufacturing techniques cannot yet replicate nature's complex design, attempts to create synthetic scaffolds have been unsuccessful.

 

“If we can make a good lung for people, we can also make a good model for injury,” Nichols said. “We can create a fibrotic lung, or an emphysematous lung, and evaluate what’s happening with those, what the cells are doing, how well stem cell or other therapy works. We can see what happens in pneumonia, or what happens when you’ve got a hemorrhagic fever, or tuberculosis, or hantavirus — all the agents that target the lung and cause damage in the lung.”

(Source: huliq.com:Photographer unknown)

The researchers have already begun work on large-scale experiments, “decellularizing” pig lungs with an eye toward using them to produce larger samples of lung tissue that could lead to applications in humans. They’re also taking on the challenge of vascularization — stimulating the growth of blood vessels that will enable the engineered tissues to survive outside the special bioreactors that the researchers now use to keep them alive by bathing them in a life-sustaining cocktail of nutrients and oxygen.

Technical and scientific challenges remain such as finding ways of creating stem cells—which can transform into any other type of cell—from patients with lung disease. No techniques currently exist for creating such cells, which would carry no risk of immune rejection.

Niklason estimates it will be about 20 to 25 years before her team's technique can be used in humans.

Researchers from the University of Texas Medical Branch at Galveston have demonstrated a potentially revolutionary solution to this problem. As they describe in an article published electronically ahead of print by the journal Tissue Engineering Part A, they seeded mouse embryonic stem cells into “acellular” rat lungs — organs whose original cells had been destroyed by repeated cycles of freezing and thawing and exposure to detergent. 

“People ask us why we’re doing the lung, because it’s so hard,” said Dr. Joaquin Cortiella, one of the article’s lead authors. “But the potential is so great, and the technology is here. It’s going to take time, but I think we’re going to create a system that works.”

The new research represents a "real leap forward" in lung regeneration, said Peter Lelkes, a biomedical engineer at Drexel University in Philadelphia. "People have engineered organs such as bone and cartilage before, but by comparison to the lung, these are all kids' games," added Lelkes, who was not involved with the study.